17-28759337-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077498.3(FAM222B):c.622T>G(p.Leu208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM222B NM_001077498.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14621317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM222B	NM_001077498.3	c.622T>G	p.Leu208Val	missense_variant	3/3	ENST00000581407.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM222B	ENST00000581407.6	c.622T>G	p.Leu208Val	missense_variant	3/3	1	NM_001077498.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.622T>G (p.L208V) alteration is located in exon 4 (coding exon 2) of the FAM222B gene. This alteration results from a T to G substitution at nucleotide position 622, causing the leucine (L) at amino acid position 208 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	17
Dann	Benign	0.94
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;.;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Uncertain	0.61	T
REVEL	Benign	0.13
Sift4G	Benign	0.18	T;T;T;.
Polyphen		0.96	.;D;D;.
Vest4		0.39
MutPred		0.24		.;Gain of glycosylation at T205 (P = 0.1379);Gain of glycosylation at T205 (P = 0.1379);Gain of glycosylation at T205 (P = 0.1379);
MVP		0.043
MPC		0.16
ClinPred		0.32	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27086355;